DNA damage: beta zero versus beta plus thalassemia

Abstract

Background: β thalassemia results in an increase in the α to non-α chain ratio. Iron released from unpaired α chains in RBCs and that ensuing from regular transfusions is the major cause of cellular damage. The use of iron chelators to counter the iron overload is accompanied by side-effects. The extent of iron toxicity could vary from one patient to another and could help in determining the optimal chelator dose for each patient.

Aim: To observe the pro-oxidant/antioxidant disturbance and the extent of DNA damage in β thalassemia patients with different β globin gene anomalies.

Methods: The formation of Reactive Oxygen Species (ROS ) was observed by incubation of cell suspensions with 2′,7′, dichlorofluorescin-diacetate (DCFH DA) and DNA damage was demonstrated by single cell gel electrophoresis. Heinz bodies were observed by staining blood smears.

Subjects: The study group comprised 50 regularly transfused beta thalassemia patients and 40 non thalassemic controls.

Results: While Heinz bodies and nucleated RBCs were seen in all the patients, oxidation of DCFH and DNA damage were seen to be associated with the β globin gene defect. DNA damage was found to be greater in β⁰ homozygotes as compared to the β⁺ homozygotes, and was maximum in patients presenting with the 619 base pair deletion.

Conclusion: In the present study, iron toxicity, as indicated by DNA damage, has been seen to vary in the patients. Thus, monitoring of the dose of iron chelators, according to the type of mutation in the beta globin gene, may help improve the compliance of beta thalassemics to chelation therapy and prevent side-effects in patients with beta plus mutations.

• Alpha chain toxicity
• DCFH
• oxidative stress

Acknowledgements

The authors are deeply indebted to the entire staff of the blood bank at Jaya Arogya Hospitals for extending their co-operation in providing blood drawn for cross-matching prior to transfusion of the patients.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

The authors acknowledge the University Grants Commission and the Indian Council of Medical Research for providing funds for consumables. Rakesh Kumar also received a senior research fellowship from the ICMR.